Diethyl Ether → 1-{1-[1(4-Chlorophenyl)ethyl]azetidin-3-ylidene}-1-(3,5difluorophenyl)-2-methylpropan-2-ol

HRID 602672Notes

Reaction equation

HRID 602672 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:13][CH:12]([CH:14]([C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=3)C(OC)=O)[CH2:11]2)[CH3:9])=[CH:4][CH:3]=1.[CH3:27][Li].CC[O:31][CH2:32][CH3:33]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:10]2[CH2:11][C:12](=[C:14]([C:19]3[CH:24]=[C:23]([F:25])[CH:22]=[C:21]([F:26])[CH:20]=3)[C:32]([CH3:33])([OH:31])[CH3:27])[CH2:13]2)[CH3:9])=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 3283Diethyl Ether2×HCID 86609768Methyl {1-[1-(4-chlorophenyl)ethyl]azetidin-3-yl}(3,5-difluorophenyl)acetateHCID 178418348HCID 178418348, compound

Product 1

HCID 114062781-{1-[1(4-Chlorophenyl)ethyl]azetidin-3-ylidene}-1-(3,5difluorophenyl)-2-methylpropan-2-ol

Conditions

Temperature
-78 °C

Procedure

A solution of 0.02 mg (0.53 mmol) of methyl {1-[1-(4-chlorophenyl)ethyl]azetidin-3-yl}(3,5-difluorophenyl)acetate in 2 mL ether was cooled to −78° C. under nitrogen. To this was added 0.8 mL of a 1.6 M solution of methyllithium in ether and the solution was stirred at −78° C. After 1 h, the solution was quenched by addition of 1 mL water and the mixture was partitioned between 10 mL ether and 2 mL water. The aqueous layer was washed two times with 10 mL ethyl acetate and the combined organic extracts were dried over Na2SO4 and concentrated. The residue was purified by reverse phase chromatography (Waters Xterra C18, 19 mm×10 mm) using a gradient of CH3CN—H2O-Et3N (20:80:0.1 to 60:40:0.1). Homogenous fractions were pooled and concentrated to afford the title compound. 1NMR (CDCl3) δ 1.23 (s, 3H), 1.35 (s, 3H), 1.36 (s, 3H), 6.6446.74 (m, 3H), 7.24-7.32 (m, 4H); Mass Spectrum: m/e=378 (M+1 35Cl) and 380 (M+1 35Cl).

Workup

  1. customthe solution was quenched by addition of 1 mL water
  2. customthe mixture was partitioned between 10 mL ether and 2 mL water
  3. washThe aqueous layer was washed two times with 10 mL ethyl acetate
  4. dry with materialthe combined organic extracts were dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by reverse phase chromatography (Waters Xterra C18, 19 mm×10 mm)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-dbefa5fdc2584e14bc72e71dacbb39a8
Source dataset
uspto-grants-2011_03
Patent number
US07906503B2

Reaction notes

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